Since the outbreak of the new coronary pneumonia, virus "mutation" has always been a topic of concern. So far, many research institutions have started researching this.
What does viral mutation mean? Will it cause changes in pathogenic mechanisms and pose challenges to the development and use of drugs and vaccines? This has become an issue of concern.
Although many people are concerned about "viral mutations," Red Star News quoted experts as saying that mutations in new coronaviruses are very limited.
Yang Zhanqiu, director of the Institute of Virology, Wuhan University School of Medicine, said that at present, the mutations of the new coronavirus are small and have little impact on drug design and detection reagents.
At the same time, virus mutations can be used to determine the intergenerational relationship of the virus, so as to find the source of the disease.
On March 6, the World Health Organization encouraged countries to provide virus samples to verify mutations through the media. On the same day, Zhou Qi, deputy secretary general of the Chinese Academy of Sciences and academician of the Chinese Academy of Sciences, said that there may have been some reports about the mutation of the virus so far, but more cases and more depth are needed for further study.
Zhou Qi said, "At present, there is a unified deployment of virus mutations and vaccine development in China, and the virus mutations we have seen have not affected drug development, antibody preparation and vaccine preparation."
Multiple papers focus on whether the virus is mutated
"Virus mutation", at first glance, is a bit scary, and it may even cause people to have terrible associations. But if you understand the relevant knowledge, you will know that "mutations" occur all the time in the biological world. This is a "neutral word."
"Viruses, animals, plants, etc. are changing all the time." Dr. Qu Mingsheng, Department of Microbiology, School of Basic Medicine, Anhui Medical University, said in an interview with Red Star News.
"During our conversation, the cells in our body may be mutated. As long as the cells are proliferating, there is a possibility of mutation. However, the probability of mutation in human cells is lower because DNA is a double-stranded structure, which is relatively complex, and Can be corrected in most cases. "
Qu Mingsheng said that as a simple living body, viruses are prone to errors during replication. But this is only relative to humans. DNA is susceptible to changes during viral replication, leading to changes in protein encoding.
There are also classifications in viruses. DNA viruses are relatively stable compared to RNA viruses. For example, hepatitis B virus is a virus that does not change easily.
The new coronavirus is an RNA virus. The single-stranded structure of RNA determines that errors will be retained if errors occur during replication.
For example, influenza and HIV viruses have a relatively high chance of mutation in RNA viruses. Similarly, new coronaviruses are RNA viruses.
According to the National Business Daily report, on February 18, scholars at Yale University and the University of Sydney published an article stressing that when the virus is transmitted between different hosts, mutations will inevitably occur, but mutation does not mean that the virus will be abnormal and destructive New virus features.
On February 29, Brazilian and British scientists published a paper, "The First Report of a New Coronavirus in South America," and mentioned that researchers took two Brazilian patients with a new type of coronary pneumonia in Italy who have traveled in Italy as their research subjects, and analyzed their viral genes. Later, it was found that the virus genome of one of them had three mutation points compared with the "Hu-1 reference strain" published in China, and two cases of the new coronavirus had two different virus sources.
So has the new coronavirus mutated? According to the online popular science magazine "Return to Park", on February 19th, a study uploaded by the Xishuangbanna Tropical Botanical Garden of the Chinese Academy of Sciences in the preprint ChinaXiv analyzed the genome data of 93 samples and found that only 120 nucleotide sites were mutated, and these mutations were uniform. Scattered over 10 coding regions.
On February 25, Southern Medical University analyzed and compared the genetic sequences of 38 strains of viruses and found that using the earliest determined sequence as a reference, there were a total of 117 site mutations. The mutation sites were not clustered and were relatively evenly distributed throughout the genome.
At the same time, the research team of Cheng Genhong of the University of California, Los Angeles, and Tan Wenjie, a researcher at the Centers for Disease Control and Prevention of the Chinese Center for Disease Control and Prevention, published an article entitled "Mutations in the Evolution of New Coronaviruses, "Recombination and insertion" research.
The research team collected and analyzed 120 new coronavirus genome sequences, including the newly collected strain genome sequences from 11 Chinese patients.
The phylogenetic tree constructed by the study indicates that the differences in gene sequences between different strains are very limited. The new coronavirus, which has 30,000 bases, mutates only a few bases.
According to The Paper, the article "About the Origin and Persistence of SARS-CoV-2" published in the "National Science Review" in cooperation with Lu Jian's group of Peking University and Cui Jie's group of Shanghai Pasteur Institute of Chinese Academy of Sciences. evolution".
The paper analyzed the genome evolution of 103 novel coronaviruses, the largest so far, and found that 149 mutations have occurred in the virus strains, and most of them have been generated recently.
The study revealed that new coronaviruses have evolved into two subtypes, L and S. Of these, 101 belong to these two subtypes. In terms of proportion, the L subtype reached 70% and the S subtype accounted for 30%.
The author of the paper believes that, based on the evolution of the new coronavirus, there may be a large difference in the transmission ability and severity of disease of the L and S subtypes.
The paper states that the difference between the two subtypes is at the 28144 position of the viral RNA genome. The L subtype is the T base (corresponding to leucine, Leu), and the S subtype is the C base (corresponding to serine, Ser).
By comparing with other coronaviruses, the authors found that the new S-type coronavirus is closer to the bat-derived coronavirus on the evolutionary tree and concluded that the S-type is relatively older.
The L subtype was more common in the early stages of the Wuhan outbreak, and the frequency of the L subtype decreased after early January 2020. The authors believe that human intervention may exert greater selective pressure on the L subtype, and without these interventions, the L subtype may be more aggressive and spread faster.
On the other hand, because the selection pressure is relatively weak, the older and less aggressive S-types may have increased in relative frequency.
These findings mean that there is an urgent need to conduct further comprehensive studies combining genomic data, epidemiological data, and chart records of clinical symptoms of patients with coronavirus disease in 2019.
The above studies have attracted much attention because the mutations of the virus have produced different subtypes of new coronaviruses with different infectivity.
However, some experts have expressed different opinions on the division of virus subtypes in this study.
On March 6, Yang Zhanqiu, director of the Institute of Virology and PhD supervisor at Wuhan University School of Medicine, said in an interview with Red Star News that the general mutation of a virus can be considered to be a subtype. The proportion of mutations in the new coronavirus is small.
Qu Mingsheng also said that in the new coronavirus genome of 30,000 bases, one, several, dozens, or hundreds of nucleotide changes may be common. This is not a big mutation, it can only be said to be a mutation.
"Similarly, it cannot be determined based on the number of nucleotide mutations that it is a new subtype. It must be changed according to the detection antigen of the virus and the adaptability of the host in order to be able to say that a new subtype appears."
Virus mutation is mainly determined by internal factors
There are three differences between the new coronavirus in Brazilian patients who have not been to China and the virus gene published in Wuhan. Does it prove that the virus is more susceptible to mutation when transmitted between different regions and races?
Qu Mingsheng explained that the mutation of the virus is determined by internal factors, and external factors induce induction.
The internal causes of viral mutation are the characteristics of the virus itself, including whether its genomic structure is DNA or RNA, and how the virus replicates.
Qu Mingsheng said, but compared to influenza and HIV, the chance of coronavirus mutation is relatively low.
For external reasons, the spread of the virus in different hosts easily causes mutations. "For example, between different species, humans, bats, and pangolins, there are great differences in terms of body temperature alone. In order to adapt to the host environment, the virus will mutate itself."
Qu Mingsheng said that between different populations, because of the differences in population immunity, some populations have strong immunity, the virus is subject to selection pressure, and mutations also occur.
Other viruses mutate due to the pressure of drugs. "But even without these external causes, the virus will mutate in the epidemic of nature. But this mutation is a random process and there is no targeted screening."
Yang Zhanqiu believes that the structure and host of the virus are two important factors that affect the mutation of the virus, and changes in the natural environment also have a certain effect on the mutation of the virus.
So is the ethnic difference between Brazilian patients and Chinese patients the main reason for the mutation?
Qu Mingsheng said that mutations in the virus during transmission are normal. As long as foreign patients still use Chinese primers designed to detect the virus, it means that there is not much mutation in the virus.
Can the trend of virus mutations be predicted? Yang Zhanqiu said that the mutation trend of the virus is also related to the structure of the virus and its host. At present, the mutation of the new coronavirus is not fast, and genetic recombination is even more impossible.
What are the effects of virus mutations?
So does the mutation of the new coronavirus affect the patient's symptoms? Qu Mingsheng believes that this possibility exists:
Sometimes a key nucleotide or key protein of a virus may have a change in its encoded nucleotide position, which will cause its key amino acid to change.
It may change the virus from low pathogenicity to high pathogenicity. There is such a possibility for influenza viruses, and certainly for coronaviruses.
But so far no reports have been found in this regard.
However, it is difficult to draw conclusions from the study of the virus structure itself. Yang Zhanqiu believes that the virus of patients with different symptoms can be analyzed.
So does viral mutation pose a challenge to existing medications? In particular, it is aimed at whether some target drugs will cause loss of efficacy. Qu Mingsheng believes that only very large mutations in the virus can change the receptor and target.
From the current point of view, the possibility of such a degree of variation is extremely low. But virus mutations may bring some challenges to the use of vaccines. "The difficulty in developing vaccines for influenza and HIV is that viruses often mutate."
Yang Zhanqiu also believes that the mutation of the virus mainly affects the vaccine. However, it has little effect on drug design because small molecule peptides are targeted at a certain target of the virus, but most drugs are targeted at the entire virus rather than at a specific gene or part of the virus.
Similarly, the current degree of mutation of new coronaviruses will not cause the virus's antigenic reagents and nucleic acid reagents to fail.
In response to the "false negative" or "return to positive" situation in various places, Yang Zhanqiu believes that the reason may be related to the sampling of the test. Although the patient may have no symptoms, the virus still exists in the body. The sampling method causes inaccurate test results.
At the press conference on the joint prevention and control of the State Council on March 6, Zhou Qi, deputy secretary-general of the Chinese Academy of Sciences and an academician of the Chinese Academy of Sciences, said that the mutation of the virus may present some challenges. More cases are needed and more in-depth research is needed.
"At present, there is a unified deployment of virus mutation and vaccine research and development in China, and the virus mutations we have seen have not affected drug development, antibody preparation and vaccine preparation." Zhou Qi said that he is actively observing the degree of virus mutation and is actively Geographical layout research projects.
Virus mutation monitoring requires multinational collaboration
In a paper published by Cheng Genhong, a professor of the Department of Microbiology and Immunogenetics at the University of California, Los Angeles, and Tan Wenjie, a researcher at the Centers for Disease Control and Prevention of the Chinese Center for Disease Control and Prevention, mentioned that in order to further confirm the genetic mutation of the new coronavirus, the researchers obtained 120 new coronavirus genome sequences uploaded on the influenza virus data platform GISAID.
At present, the monitoring of virus mutations is mainly performed by comparing gene sequences. Qu Mingsheng told Red Star News that scientists around the world now have an open public platform. After research institutions find new species, viruses, and bacteria, scientists will upload their nucleic acid sequences to the Internet for other scientific research around the world. People come to learn, to understand, to refer to this thing.
So when people in different countries find the virus circulating in their own country, they will compare its gene sequence with the data on the Internet.
In a response to the National Business Daily interview on March 6, the World Health Organization called for all countries with confirmed cases to provide more viral gene sequences in order to jointly conduct research on viral mutations.
At the same time, according to the mutation of the virus, it can be used to determine the intergenerational relationship of the virus and find the source of the virus.
On February 20, researcher Yu Wenbin of the Xishuangbanna Tropical Botanical Garden of the Chinese Academy of Sciences stated in the official website of the Botanical Garden that Xishuangbanna Tropical Botanical Garden of the Chinese Academy of Sciences, together with researchers from South China Agricultural University and the Beijing Brain Center, collected all areas of the world and shared them into the GISAID EpiFluTM database It covers the genome data of 93 new coronavirus samples from 12 countries on four continents (as of February 12). Through the analysis of the whole genome data, the source of infection and the path of spread can be traced.
The study found that 93 samples received contained 58 haplotypes. The haplotypes of patients from the South China seafood market were related to H1, while the more ancient gene types H3, H13, and H38 were from outside the South China seafood market.
It can be seen that the new coronavirus in the South China seafood market was introduced from other places and spread rapidly outside the market.
At present, researchers around the world are still researching virus mutations and virus traceability.
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